c-Met is a receptor for hepatocyte growth factor (HGF). HGF is a cytokine that binds the extracellular region of the c-Met receptor tyrosine kinase to induce mitogenesis, movement, morphogenesis, and angiogenesis in various normal cells and tumor cells. c-Met is a representative receptor tyrosine kinase existing on the surface of cells, is itself a proto-oncogene, and is sometimes involved in various mechanisms related to cancer, such as cancer development, metastasis, migration, invasion, and angiogenesis, independent from a ligand (e.g., HGF). Thus, c-Met recently has been emerging as a new target for anti-cancer therapy.
In particular, c-Met is known to be involved in induction of resistance to commonly used anti-cancer drugs and, thus, is regarded as important with respect to personalized treatments. Representative anti-cancer therapeutic drugs targeting epidermal growth factor receptor (EGFR) (also known as ERBB1), such as ERBITUX™ (cetuximab) and TARCEVA™ (erlotinib), work by blocking the transduction of signals related to a cancer development mechanism. In addition, HERCEPTIN™ (trastuzumab), which is well known as a breast cancer therapeutic drug, targets ERBB2 (HER2) and works by blocking the transduction of signals necessary for cell proliferation.
Recent reports indicate that some patients are resistant to the drugs described above due to the overexpression of c-Met protein, wherein transduction of other signals that induce cell proliferation is activated. Thus, to many drug companies, c-Met has emerged as a target molecule for anti-cancer drugs.
The related art discloses antibody therapeutic drugs that inhibit the function of c-Met. However, in this related art, the antibody induces dimerization of c-Met molecules, thereby causing cancer.
In another related art, which discloses an antibody therapeutic drug inhibiting the function of c-Met, the antibody is capable of inhibiting the binding of c-Met to HGF c-Met, which is a c-Met ligand, but the binding of the antibody to c-Met induces the dimerization of c-Met, independent from the ligand. As a result, the antibody acts as an agonist that induces the transduction of cancer-causing signals.
Another related art discloses, to prevent the dimerization of c-Met, a one-armed antagonistic antibody of c-Met, which is prepared by modifying an agonist, and a two-armed antibody using a genetic recombinant method. Product development in clinical trials is currently in the pipeline. However, even in this related art, the antibody works only when the treatment is performed together with chemical therapy. When the antibody is independently treated, anti-cancer therapeutic effects are proven to be low.
Therefore, there is still a need to develop a new pharmaceutical composition for preventing and treating cancer that inhibits the function of c-Met.